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3D 打印可组装定制支架作为用于特定部位再生医学的多功能微凝胶载体。

A 3D-Printed Assemblable Bespoke Scaffold as a Versatile Microcryogel Carrier for Site-Specific Regenerative Medicine.

机构信息

Institute for Biomechanics, Department of Health Sciences and Technology, ETH Zurich, Zurich, 8092, Switzerland.

Complex Materials, Department of Materials, ETH Zurich, Zurich, 8093, Switzerland.

出版信息

Adv Mater. 2023 Nov;35(44):e2302008. doi: 10.1002/adma.202302008. Epub 2023 Sep 24.

Abstract

Advances in additive manufacturing have led to diverse patient-specific implant designs utilizing computed tomography, but this requires intensive work and financial implications. Here, Digital Light Processing is used to fabricate a hive-structured assemblable bespoke scaffold (HIVE). HIVE can be manually assembled in any shape/size with ease, so a surgeon can create a scaffold that will best fit a defect before implantation. Simultaneously, it can have site-specific treatments by working as a carrier filled with microcryogels (MC) incorporating different biological factors in different pockets of HIVE. After characterization, possible site-specific applications are investigated by utilizing HIVE as a versatile carrier with incorporated treatments such as growth factors (GF), bioceramic, or cells. HIVE as a GF-carrier shows a controlled release of bone morphogenetic protein/vascular endothelial growth factor (BMP/VEGF) and induced osteogenesis/angiogenesis from human mesenchymal stem cells (hMSC)/human umbilical vein endothelial cells (HUVECs). Furthermore, as a bioceramic-carrier, HIVE demonstrates enhanced mineralization and osteogenesis, and as a HUVEC carrier, it upregulates both osteogenic and angiogenic gene expression of hMSCs. HIVE with different combinations of MCs yields a distinct local effect and successful cell migration is confirmed within assembled HIVEs. Finally, an in vivo rat subcutaneous implantation demonstrates site-specific osteogenesis and angiogenesis.

摘要

增材制造技术的进步使得利用计算机断层扫描技术制造出各种个性化的植入物设计成为可能,但这需要大量的工作和资金投入。在这里,我们使用数字光处理技术来制造一种具有蜂巢结构的可组装定制支架(HIVE)。HIVE 可以轻松地手动组装成任何形状/大小,因此外科医生可以在植入前创建最适合缺损的支架。同时,它可以作为一种填充有微凝胶(MC)的载体,在 HIVE 的不同口袋中加入不同的生物因子,从而实现特定部位的治疗。在进行特征描述后,我们研究了 HIVE 作为一种多功能载体的可能的特定部位应用,载体中加入了不同的治疗方法,如生长因子(GF)、生物陶瓷或细胞。作为 GF 载体,HIVE 显示出骨形态发生蛋白/血管内皮生长因子(BMP/VEGF)的控制释放,并从人骨髓间充质干细胞(hMSC)/人脐静脉内皮细胞(HUVEC)中诱导成骨/血管生成。此外,作为生物陶瓷载体,HIVE 表现出增强的矿化和成骨作用,作为 HUVEC 载体,它上调 hMSC 的成骨和成血管基因表达。HIVE 与 MC 的不同组合产生了明显的局部效应,并证实了组装后的 HIVE 内有细胞的迁移。最后,在大鼠皮下植入的体内实验中证明了特定部位的成骨和血管生成。

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